Health monitoring of wildlife in France : SAGIR network and epidemiological monitoring of chiroptera rabies

Two wildlife surveillance networks centralised at AFSSA-LERRPAS are presented. SAGIR network is a generalist network monitoring wildlife diseases in France. Collected data also provide information on the potential reservoir or vector status of wild animals for pathogens transmissible to man or domestic animals. The use of this network to monitor avian influenza in wild birds in France is described. The bat rabies monitoring network specialises in one disease and it must take into account the protected status of bats.Deux réseaux de surveillance de la faune sauvage centralisés à l'AFSSA-LERRPAS sont présentés. Le réseau SAGIR est un réseau généraliste de surveillance et d'alerte des maladies de la faunesauvage en France. Les données recueillies permettent aussi de connaître le statut potentiel de réservoir ou de vecteur des animaux sauvages vis-à-vis de certains agents pathogènes transmissibles à l'homme ou aux animaux domestiques. L'utilisation de ce réseau comme moyen de surveillance de l'influenza aviaire chez les oiseaux sauvages est détaillée. Le réseau de surveillance de la rage des chauves-souris est consacré à une seule maladie. Le fonctionnement doit prendre en compte le statut protégé des espèces suivies

Tularemia : situation in france, issues and public health risk

This is a retrospective study on natural foci of tularemia in animals as well as human cases reported in France between 1999 and 2004. Since 1999, approximately 20 to 60 animals foci of infection in hares are detected every year in 19 to 34 French departments. Human cases often occur in areas where animal foci have erupted, but not always. There are several reasons explaining the presence of this disease on French territory, its underestimation in animals, and probably in man, and its durability. The disease is generally poorly recognised, except amongst shooters who are aware of its existence. Several clinical forms are known in man, sometimes with severe symptoms. The diagnosis of tularemia can be difficult due to its non-specific clinical features. Tularemia is mostly described in hares but other species can be also affected, serving as reservoirs for the infection and sometimes acting as vectors as well. The animal population tested for tularemia should be widened to include other wild species, as well as some of our domestic animals. In man, this diagnosis should be considered in people presenting certain clinical signs. A background on epidemiological data is given. In addition, as Francisella tularensis is one of the bioterrorism agents, it is essential that clinicians and biologists recognise this bacteria and are aware of its dangers. Tularemia was removed from the list of Legally Contagious Disease in veterinary medicine in 1996. It has become a notifiable disease in human medicine in 2002.Il s’agit d’une étude rétrospective de foyers animaux de la tularémie et des cas de contamination humaine recensés en France entre 1999 et 2004. Depuis 1999, environ 20 à 60 foyers sont identifiés chaque année chez des lièvres, dans 19 à 34 départements français. Les cas humains se déclarent souvent dans les régions où sont détectés les cas animaux, mais pas toujours. Plusieurs raisons sont à l’origine de la présence de la maladie sur le territoire, de sa sous-estimation chez les animaux, et vraisemblablement aussi chez l’homme, et de sa pérennité. La maladie est généralement mal connue, sauf chez les chasseurs qui en sont informés. Elle se présente sous de multiples formes chez l’homme et peut occasionner des troubles assez graves. Le diagnostic clinique peut être difficile, à cause des symptômes relativement peu spécifiques. Le lièvre n’est pas la seule espèce animale en cause, il n’est qu’un révélateur d’un foyer de la maladie. Plusieurs autres espèces y sont sensibles et constituent des réservoirs d’infection, certaines jouant également un rôle de vecteur. Il faudrait élargir la recherche de la tularémie à d’autres espèces de la faune sauvage, mais aussi à certaines espèces domestiques. Chez l’homme, cette maladie potentiellement grave devrait faire l’objet d’une recherche systématique face à certains symptômes cliniques. Plusieurs facteurs épidémiologiques sont rappelés. Par ailleurs, Francisella tularensis faisant partie des agents du bioterrorisme, il est essentiel que les cliniciens et les biologistes apprennent à reconnaître cette bactérie et exercent une certaine vigilance. La tularémie ne fait plus partie des Maladies Légalement Contagieuses en médecine vétérinaire depuis 1996. Elle est à déclaration obligatoire en santé humaine depuis 2002

Repurposing of Drugs as Novel Influenza Inhibitors From Clinical Gene Expression Infection Signatures

Influenza virus infections remain a major and recurrent public health burden. The intrinsic ever-evolving nature of this virus, the suboptimal efficacy of current influenza inactivated vaccines, as well as the emergence of resistance against a limited antiviral arsenal, highlight the critical need for novel therapeutic approaches. In this context, the aim of this study was to develop and validate an innovative strategy for drug repurposing as host-targeted inhibitors of influenza viruses and the rapid evaluation of the most promising candidates in Phase II clinical trials. We exploited in vivo global transcriptomic signatures of infection directly obtained from a patient cohort to determine a shortlist of already marketed drugs with newly identified, host-targeted inhibitory properties against influenza virus. The antiviral potential of selected repurposing candidates was further evaluated in vitro, in vivo, and ex vivo. Our strategy allowed the selection of a shortlist of 35 high potential candidates out of a rationalized computational screening of 1,309 FDA-approved bioactive molecules, 31 of which were validated for their significant in vitro antiviral activity. Our in vivo and ex vivo results highlight diltiazem, a calcium channel blocker currently used in the treatment of hypertension, as a promising option for the treatment of influenza infections. Additionally, transcriptomic signature analysis further revealed the so far undescribed capacity of diltiazem to modulate the expression of specific genes related to the host antiviral response and cholesterol metabolism. Finally, combination treatment with diltiazem and virus-targeted oseltamivir neuraminidase inhibitor further increased antiviral efficacy, prompting rapid authorization for the initiation of a Phase II clinical trial. This original, host-targeted, drug repurposing strategy constitutes an effective and highly reactive process for the rapid identification of novel anti-infectious drugs, with potential major implications for the management of antimicrobial resistance and the rapid response to future epidemic or pandemic (re)emerging diseases for which we are still disarmed

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Environmental factors associated with the seroprevalence of <i>Toxoplasma gondii</i> in Wild Boars (<i>Sus scrofa</i>), France

International audienceToxoplasma gondii is a protozoan parasite infecting humans and animals. Wild boars Sus scrofa are a potential source of human infection and an appropriate biological model for analyzing T. gondii dynamics in the environment. Here, we aimed to identify environmental factors explaining the seroprevalence of toxoplasmosis in French wild boar populations. Considering 938 individuals sampled from 377 'communes', overall seroprevalence was 23% (95% confidence interval: [22-24]). Using a Poisson regression, we found that the number of seropositive wild boars detected per 'commune' was positively associated with the presence of European wildcats (Felis silvestris) and moderate winter temperatures

Ecological and biological factors involved in the transmission of Echinococcus multilocularis in the French Ardennes.

International audienceIn order to identify the respective importance of the ecological and biological factors involved in the transmission of Echinococcus multilocularis, we estimated grassland vole intermediate host (Microtus sp. and Arvicola terrestris) population densities, in relation to the diet of the definitive host (red fox, Vulpes vulpes) and with the prevalence of E. multilocularis in the fox population. The study was conducted in the Ardennes, north-eastern France, which is an area with a high incidence of alveolar echinococcosis. Surface index methods showed that Microtus was the most abundant intermediate host in the area. Furthermore, Microtus was present in one-third of the 144 faeces and 98 stomach content samples examined and represented more than two-thirds of the rodent occurrences. Red fox predation on Microtus was significantly correlated with Microtus relative abundance. In contrast, the relative abundance of A. terrestris was very low. This species, as well as Clethrionomys glareolus and Apodemus sp., was little consumed. E. multilocularis prevalence in foxes was determined from carcasses and reached 53% (95% confidence interval 45-61%). Intensity of infection varied from 2 to 73,380 worms per fox, with 72% of the sampled worm burden harboured by 8% of the sampled foxes. The selected explanatory variables (sex, year, age class, health and nutritional condition, and season) failed to predict prevalence rate and worm burden. The high prevalence rate in foxes indicates the possibility of intense E. multilocularis transmission, apart from periods, or in landscapes, favourable to large population outbreaks of grassland rodents

Avian Cell Line DuckCelt®-T17 Is an Efficient Production System for Live-Attenuated Human Metapneumovirus Vaccine Candidate Metavac®

The development of a live-attenuated vaccine (LAV) for the prevention of human metapneumovirus (HMPV) infection is often hampered by the lack of highly efficient and scalable cell-based production systems that support eventual global vaccine production. Avian cell lines cultivated in suspension compete with traditional cell platforms used for viral vaccine manufacture. We investigated whether the DuckCelt®-T17 avian cell line (Vaxxel), previously described as an efficient production system for several influenza strains, could also be used to produce a new HMPV LAV candidate (Metavac®, SH gene-deleted A1/C-85473 HMPV). To that end, we characterized the operational parameters of MOI, cell density, and trypsin addition to achieve the optimal production of Metavac®, and demonstrated that the DuckCelt®-T17 cell line is permissive and well-adapted to the production of the wild-type A1/C-85473 HMPV and the Metavac® vaccine candidate. Moreover, our results confirmed that the LAV candidate produced in DuckCelt®-T17 cells conserves its advantageous replication properties in LLC-MK2 and 3D-reconstituted human airway epithelium models, and its capacity to induce efficient neutralizing antibodies in a BALB/c mouse model. Our results suggest that the DuckCelt®-T17 avian cell line is a very promising platform for the scalable in-suspension serum-free production of the HMPV-based LAV candidate Metavac®

Protocol for a partially nested randomised controlled trial to evaluate the effectiveness of the scleroderma patient-centered intervention network COVID-19 home-isolation activities together (SPIN-CHAT) program to reduce anxiety among at-risk scleroderma patients

International audienceObjective: Contagious disease outbreaks and related restrictions can lead to negative psychological outcomes, particularly in vulnerable populations at risk due to pre-existing medical conditions. No randomised controlled trials (RCTs) have tested interventions to reduce mental health consequences of contagious disease outbreaks. The primary objective of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Trial is to evaluate the effect of a videoconference-based program on symptoms of anxiety. Secondary objectives include evaluating effects on symptoms of depression, stress, loneliness, boredom, physical activity, and social interaction.Methods: The SPIN-CHAT Trial is a pragmatic RCT that will be conducted using the SPIN-COVID-19 Cohort, a sub-cohort of the SPIN Cohort. Eligible participants will be SPIN-COVID-19 Cohort participants without a positive COVID-19 test, with at least mild anxiety (PROMIS Anxiety 4a v1.0 T-score >= 55), not working from home, and not receiving current counselling or psychotherapy. We will randomly assign 162 participants to intervention groups of 7 to 10 participants each or waitlist control. We will use a partially nested RCT design to reflect dependence between individuals in training groups but not in the waitlist control. The SPIN-CHAT Program includes activity engagement, education on strategies to support mental health, and mutual participant support. Intervention participants will receive the 4-week (3 sessions per week) SPIN-CHAT Program via video-conference. The primary outcome is PROMIS Anxiety 4a score immediately post-intervention.Ethics and dissemination: The SPIN-CHAT Trial will test whether a brief videoconference-based intervention will improve mental health outcomes among at-risk individuals during contagious disease outbreak